CN-122006650-A - Acylation green reaction method based on mechanochemistry

CN122006650ACN 122006650 ACN122006650 ACN 122006650ACN-122006650-A

Abstract

The invention provides a mechanochemical-based acylation green reaction method which comprises the following steps of sequentially adding mechanical conduction medium beads and reaction raw materials into a reaction container, sealing the reaction container after the addition is completed, placing the reaction container into an oscillator, starting the oscillator under the condition of room temperature, closing the oscillator after reacting for 2-20 min, taking out the reaction container, adding ice water into the cooled reaction container for quenching reaction, then filtering and separating the mechanical conduction medium beads and products, washing solids for 2-3 times by cold water in the filtering and sucking process, then compacting and drying to obtain a mixture of solid crude products and the mechanical conduction medium beads, dissolving the mixture of the solid crude products and the mechanical conduction medium beads by using a refining solvent, filtering and separating the mechanical conduction medium beads, and refining filtrate to obtain a refined product. The invention innovatively adopts mechanochemical energy to replace an external heat source, realizes molecular-level mixing and activation by high-speed oscillation at room temperature, greatly reduces energy consumption and shortens reaction time.

Inventors

ZHONG WENWU
WANG MENG
TANG QIAN
TAN TAO

Assignees

重庆医药高等专科学校

Dates

Publication Date: 20260512
Application Date: 20260130

Claims (8)

1. A mechanochemical-based green reaction process comprising the steps of: (1) Sequentially adding mechanical conductive medium beads and reaction raw materials into a reaction container, and sealing the reaction container after the addition is finished; (2) Placing the reaction container in an oscillator, setting the rotating speed to be 1500-3000 r/min, starting the oscillator at room temperature, closing the oscillator after reacting for 2-20 min, and then taking out the reaction container; (3) Crude product separation, namely adding ice water into a cooled reaction container for quenching reaction, then filtering and separating mechanical conductive medium beads and products, washing solid for 2-3 times by cold water in the filtering process, and then compacting and pumping to obtain a mixture of the solid crude product and the mechanical conductive medium beads; (4) And (3) refining the product, namely dissolving the mixture of the solid crude product and the mechanically conductive medium beads by using a refining solvent, filtering and separating the mechanically conductive medium beads, and refining the filtrate to obtain the refined product.
2. The method of claim 1, wherein the mechanically conductive beads are made of iron or stainless steel or copper or silicon nitride or zirconium oxide.
3. The mechanochemical-based acylation green reaction method according to claim 2, wherein: the mechanically conductive medium beads are made of silicon nitride.
4. The method of claim 3, wherein the mechanically conductive medium beads are spherical or rod-shaped.
5. The mechanochemical-based acylated green reaction process as claimed in any one of claims 1-4, wherein aspirin is prepared according to the following reaction steps: (1) Sequentially adding mechanical conductive medium beads, salicylic acid, a catalyst and acetic anhydride into a reaction container, and sealing the reaction container after the addition, wherein the molar ratio of the salicylic acid to the acetic anhydride is 1:1-2, and the mass ratio of the catalyst to the salicylic acid to the mechanical conductive medium beads is 0.02-0.08:1:5-7.5; (2) Placing the reaction container in an oscillator, setting the rotating speed to be 1500-3000 r/min, starting the oscillator at room temperature, reacting for 2-20 min, closing the oscillator after the fluidity of a reaction system is reduced and the color is lightened, taking out the reaction container, and putting the reaction container into an ice bath for cooling; (3) Crude product separation, namely adding ice water into a cooled reaction container for quenching reaction, then filtering and separating mechanical conductive medium beads and products, washing solid with cold water for 2-3 times in the filtering process, and then compacting and pumping to obtain a mixture of aspirin solid crude product and mechanical conductive medium beads; (4) Refining the product, namely transferring the mixture of the aspirin solid crude product and the mechanical conduction medium beads into hot ethanol, carrying out suction filtration while the mixture is hot after the mixture is completely dissolved, and collecting filtrate; (5) And drying the solid obtained by suction filtration, and obtaining an aspirin refined product after drying.
6. The method of claim 5, wherein the rotation speed of the oscillator is 3000 r/min and the oscillation time is 4min.
7. The method for green reaction of mechanochemical-based acylation according to claim 5, wherein the catalyst used for preparing the aspirin is one of concentrated sulfuric acid, ferrous chloride, ferric trichloride, aluminum trichloride and cupric chloride.
8. The mechanochemical-based acylated green reaction process as claimed in any one of claims 1-4, wherein acetaminophen is produced according to the following reaction steps: (1) Sequentially adding mechanically conductive medium beads, paracetamol, acetic anhydride and water into a reaction vessel; (2) Placing the reaction container on an oscillator, setting the rotating speed to be 1500-3000 r/min, starting the oscillator at room temperature, reacting for 2-20 min, closing the oscillator after the fluidity of a reaction system is reduced and the color is changed, and then taking out the reaction container; (3) Separating a crude product, namely adding ice water into a cooled reaction container for quenching reaction, cooling to 0-10 ℃ to precipitate crystals, filtering and separating, washing solid substances in a Buchner funnel for 2-3 times by using cold water in the filtering process, and compacting and pumping to obtain a mixture of the crude acetaminophen solid product and mechanical conductive medium beads; (4) Refining the product, namely adding purified water, naHSO 3 aqueous solution and active carbon into a mixture of the solid crude acetaminophen product and the mechanically conductive medium beads, and heating and refluxing; (5) Adding NaHSO 3 solid into a suction filtration bottle, performing suction filtration while the solid is hot, and collecting filtrate; (6) And (3) crystallizing the filtrate in an ice bath, performing suction filtration again to obtain a solid, and drying to obtain white crystalline powder, namely the refined acetaminophen product.

Description

Acylation green reaction method based on mechanochemistry Technical Field The invention relates to the technical field of fine chemical engineering and pharmaceutical synthesis, in particular to an acylation green reaction method based on mechanochemistry. Background In the fields of fine chemical industry, pharmacy and material synthesis, classical organic reactions such as esterification, acylation and the like are dependent on a traditional heat conduction heating and homogeneous catalysis system for a long time. Taking the synthesis of aspirin (acetylsalicylic acid) as an example, the traditional process generally adopts catalysts such as concentrated sulfuric acid, aluminum trichloride and the like, and the reaction is driven by external heating under the high-temperature condition. Such processes have significant technical drawbacks: The safety problem is remarkable, inflammable and explosive byproducts (such as acetic acid mixed gas) can be generated in the reaction process, potential safety hazards exist, the reaction system needs to be strictly monitored in temperature to prevent flushing or decomposition accidents caused by local overheating, and the operation difficulty is high. The energy consumption and environmental burden are serious, the reaction needs to maintain high temperature (usually 80-120 ℃) for a long time, the energy utilization efficiency is low, a large amount of acid wastewater (containing sulfate and chloride) or metal-containing wastewater (such as aluminum ion residues) is generated, the treatment steps of neutralization, precipitation and the like are needed, the environmental burden is increased, and the air pollution is easily caused if the waste gas (such as acetic acid steam) is not properly treated. Mechanochemistry, which is a green synthesis technology that directly drives chemical reactions by mechanical energy, has become a research hotspot in the chemical field in recent years. The core principle is that the reactant is activated by using the mechanical force actions such as grinding, friction, vibration and the like in a mode of destroying intermolecular acting force, generating local hot spots or free radicals and the like, so that the efficient conversion under room temperature or mild conditions is realized. The technology has the remarkable advantages of replacing the traditional heat energy input, reducing the energy consumption, improving the process safety, reducing the side reaction, improving the product purity, being applicable to a solid-liquid-gas multiphase reaction system and expanding the reaction type range. However, in the field of acylation reactions, there is still a significant gap in existing mechanochemical techniques. Disclosure of Invention Aiming at the problems in the prior art, the invention aims to provide an acylation green reaction method based on mechanochemistry, which overcomes the defects of the traditional process and realizes efficient, safe and environment-friendly acylation reaction at room temperature. In order to achieve the above object, the present invention provides a mechanochemical-based green acylation reaction method comprising the steps of: (1) Sequentially adding mechanical conductive medium beads and reaction raw materials into a reaction container, and sealing the reaction container after the addition is finished; (2) Placing the reaction container in an oscillator, setting the rotating speed to be 1500-3000 r/min, starting the oscillator at room temperature, closing the oscillator after reacting for 2-20 min, and then taking out the reaction container; (3) Crude product separation, namely adding ice water into a cooled reaction container for quenching reaction, then filtering and separating mechanical conductive medium beads and products, washing solid for 2-3 times by cold water in the filtering process, and then compacting and pumping to obtain a mixture of the solid crude product and the mechanical conductive medium beads; (4) And (3) refining the product, namely dissolving the mixture of the solid crude product and the mechanically conductive medium beads by using a refining solvent, filtering and separating the mechanically conductive medium beads, and refining the filtrate to obtain the refined product. In the scheme, the mechanically conductive medium beads are made of iron or stainless steel or copper or silicon nitride or zirconia. In the scheme, the mechanically conductive medium beads are made of silicon nitride. In the scheme, the mechanically conductive medium beads are spherical or rod-shaped. When the mechanically conductive medium beads are spherical, the diameter is preferably 3mm. Aspirin was prepared according to the following reaction steps: (1) Sequentially adding mechanical conductive medium beads, salicylic acid, a catalyst and acetic anhydride into a reaction container, and sealing the reaction container after the addition, wherein the molar ratio of the salicylic acid to the acetic anhydr